The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors

Abstract

Immune checkpoint inhibitors (CPI) are increasingly being used in oncology, and many autoimmune side effects have been described. Diabetes mellitus (DM) has been reported in approximately 1% of subjects treated with programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors, alone or in association with CTLA-4 inhibitors. In the present mini-review, we aimed to describe different clinical pictures and pathophysiology associated with these forms of diabetes. Data on CPI-related DM was gathered from the largest case series in the literature and from our centre dedicated to immunotherapy complications (ImmuCare-Hospices Civils de Lyon). Most cases are acute autoimmune insulin-dependent diabetes which are similar to fulminant diabetes (extremely acute onset with concomitant near-normal HbA1c levels). Other cases, however, have a phenotype close to type 2 diabetes or appear as a decompensation of previously known type 2 diabetes. The occurrence of diabetes can also be a complication of autoimmune pancreatitis induced by CPI use. Finally, two cases of diabetes in a context of autoimmune lipoatrophy have recently been described. Regarding the wide variety of CPI-induced diabetes, the discovery of a glucose disorder under CPI should motivate specialised care for aetiological diagnosis and appropriate treatment.

Keywords: Alpha cell pancreatic function; Anti-PD-1; Anti-PD-L1; Autoimmune diabetes; Autoimmune generalised lipoatrophy; Autoimmune lipodystrophy; Autoimmune pancreatitis; Beta cell pancreatic function; Diabetes mellitus; Exocrine pancreatic function; Fulminant diabetes; Immune checkpoint inhibitors side effects; Immunotherapy; Pancreas volume; Programmed cell death-1 (PD-1); Programmed death ligand 1 (PD-L1).